A Nanobody of PEDV S1 Protein: Screening and Expression in Escherichia coli DOI Creative Commons
Zhipeng Hao, Xufeng Dong,

Zhong-tao Zhang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1116 - 1116

Published: Sept. 4, 2024

Porcine epidemic diarrhea virus (PEDV) has caused significant economic losses to the pig farming industry in various countries for a long time. Currently, there are no highly effective preventive or control measures available. Research into pathogenic mechanism of PEDV shown that it primarily causes infection by binding S protein CD13 (APN) receptor on membrane porcine intestinal epithelial cells. The S1 region contains three neutralization epitopes and multiple receptor-binding domains, which closely related viral antigenicity ad-sorption invasion. Nanobodies type single-domain antibody have been discovered recent years. They can be expressed large scale through prokaryotic expression systems, makes them cost-effective, stable, less immunogenic. This study used phage display library nanobodies against protein. After rounds selection enrichment, DNA sequence specific nanobody S1Nb1 was successfully obtained. To obtain soluble S1Nb1, its inserted vector Pcold solubility-enhancing SUMO tag added. resulting recombinant vector, Pcold-SUMO-S1Nb1, then transformed

Language: Английский

ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6: a first-in-human study DOI

Qianyun Wu,

Yanfei Wu, You Zhang

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2024, Volume and Issue: 51(8), P. 2444 - 2457

Published: March 14, 2024

Language: Английский

Citations

19
Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors DOI Creative Commons
You Zhang, Di Zhang, Shuxian An

et al.

Research, Journal Year: 2023, Volume and Issue: 6, P. 0077 - 0077

Published: Jan. 1, 2023

Overexpression of CD47 is frequently observed in various types human malignancies, inhibiting myeloid-mediated elimination tumor cells and affecting the prognosis cancer patients. By mapping biomarker expression, immuno-positron emission tomography has been increasingly used for patient screening response monitoring. immunization alpacas with recombinant CD47, we prepared a CD47-targeting nanobody C2 developed [ 68 Ga]Ga-NOTA-C2, followed by an exploration diagnostic value CD47-expressing models including gastric-cancer patient-derived xenograft models. fusing to albumin binding domain (ABD), synthesized ABDC2, which had increased vivo half-life improved targeting properties. We further labeled ABDC2 Ga/ 89 Zr/ 177 Lu develop radionuclide theranostic pairs evaluated pharmacokinetics efficacies agents cell- Both specifically reacted high K D 23.50 84.57 pM, respectively. Ga]Ga-NOTA-C2 was radiochemical purity (99 >%, n = 4) visualized expression tumors. In comparison rapid renal clearance short both Ga]Ga-NOTA-ABDC2 Zr]Zr-DFO-ABDC2 showed prolonged circulation uptake, highest uptake occurring at 72 h post-injection. Moreover, Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed growth but associated toxicity, warranting optimization treatment schedules. Taken together, reported series nanobody-derived CD47-targeted agents, are readily translatable. Optimization translation pair may provide new prospects management solid

Language: Английский

Citations

32
ImmunoPET imaging of Trop2 in patients with solid tumours DOI Creative Commons
Wei Huang, You Zhang, Min Cao

et al.

EMBO Molecular Medicine, Journal Year: 2024, Volume and Issue: 16(5), P. 1143 - 1161

Published: April 2, 2024

Abstract Accurately predicting and selecting patients who can benefit from targeted or immunotherapy is crucial for precision therapy. Trophoblast cell surface antigen 2 (Trop2) has been extensively investigated as a pan-cancer biomarker expressed in various tumours plays role tumorigenesis through multiple signalling pathways. Our laboratory successfully developed two 68 Ga-labelled nanobody tracers that rapidly specifically target Trop2. Of the tracers, [ Ga]Ga-NOTA-T4, demonstrated excellent pharmacokinetics preclinical mouse models beagle dog. Moreover, Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) allowed noninvasive visualisation of Trop2 heterogeneous differential expression solid tumour ten with tumours. immunoPET could facilitate clinical decision-making patient stratification response monitoring during Trop2-targeted therapies.

Language: Английский

Citations

15
Single-Domain Antibody Theranostics on the Horizon DOI Open Access
Weijun Wei, Muhsin H. Younis, Xiaoli Lan

et al.

Journal of Nuclear Medicine, Journal Year: 2022, Volume and Issue: 63(10), P. 1475 - 1479

Published: July 14, 2022

Single-domain antibody (sdAb) is among the most promising vectors for developing molecular imaging tracers. Several sdAb tracers targeting human epidermal growth factor receptor 2 or programmed death ligand 1 have entered clinical practice. However, radiolabeled single-valent sdAbs generally high kidney retention, limiting their therapeutic applications. Therefore, engineering strategies such as PEGylation incorporation of renal cleavable linkers can be adapted to improve pharmacokinetics and reduce retention. In this Focus on Molecular Imaging review, we try summarize latest developments in sdAb-derived agents propose potential that used theranostic value sdAbs.

Language: Английский

Citations

36
CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin DOI Creative Commons
Jingbo Ma, Xiaolong Xu, Chunjin Fu

et al.

Biomaterials Research, Journal Year: 2022, Volume and Issue: 26(1)

Published: Sept. 30, 2022

It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in past decades. Cadherin 17 (CDH17) a membrane protein expressed cancers of digestive system. Nanobody represents novel antibody format targeted imaging and drug delivery. targeting CHD17 as an probe delivery vehicle toxin remains be explored its theragnostic potential cancer. Naïve nanobody phage library was screened against CDH17 Domain 1-3 identified nanobodies were extensively characterized with various assays. Nanobodies labeled tested vitro vivo detection. A fused PE38 evaluated inhibition vivo. Two (A1 E8) human high affinity specificity successfully obtained. These could specifically bind CDH17-positive cells. E8 lead determined tumor efficiently co-localize cells zebrafish embryos rapidly visualize mass mice within 3 h when conjugated dyes. showed excellent anti-tumor effect remarkably improved cell-derived (CDX) patient-derived xenograft (PDX) models. The immunotoxin also enhanced clinical 5-Fluorouracil. study presents strategy by CDH17. nanobody-based potentially promising modality translation

Language: Английский

Citations

33
A lateral flow immunochromatographic assay based on nanobody-oriented coupling strategy for aflatoxin B1 detection DOI

Xinyang Wang,

Tieqiang Sun,

Weili Shen

et al.

Sensors and Actuators B Chemical, Journal Year: 2023, Volume and Issue: 394, P. 134419 - 134419

Published: Aug. 10, 2023

Language: Английский

Citations

16
A few good reasons to use nanobodies for cancer treatment DOI Creative Commons
Neema Ahishakiye Jumapili, Maida Živalj, Romina Mora Barthelmess

et al.

European Journal of Immunology, Journal Year: 2023, Volume and Issue: 53(9)

Published: June 27, 2023

Abstract mAbs have been instrumental for targeted cancer therapies. However, their relatively large size and physicochemical properties result in a heterogenous distribution the tumor microenvironment, usually restricted to first cell layers surrounding blood vessels, limited ability penetrate brain. Nanobodies are tenfold smaller, resulting deeper penetration reach cells poorly perfused areas. rapidly cleared from circulation, which generates fast target‐to‐background contrast that is ideally suited molecular imaging purposes but may be less optimal therapy. To circumvent this problem, nanobodies formatted noncovalently bind albumin, increasing serum half‐life without majorly size. Finally, shown superior qualities infiltrate brain tumors as compared mAbs. In review, we discuss why these features make prime candidates therapy of cancer.

Language: Английский

Citations

15
Navigating the landscape of PD-1/PD-L1 imaging tracers: from challenges to opportunities DOI Creative Commons
Melinda Badenhorst, Albert D. Windhorst, Wissam Beaino

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: June 7, 2024

Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment. However, it is now well-known that PD-1/PD-L1 immunotherapy response inconsistent among patients. The current challenge customize treatment regimens per patient, which could be possible if expression dynamic landscape are known. With positron emission tomography (PET) imaging, image these targets non-invasively system-wide during therapy. A successful PET imaging tracer should meet specific criteria concerning target affinity, specificity, clearance rate target-specific uptake, name a few. structural profile of will define properties can used optimize tracers in development design new ones. Currently, range PD-1/PD-L1-targeting available from different molecular categories have shown impressive preclinical clinical results, each with own advantages disadvantages. This review provide an overview targeting axis. Antibody, peptide, antibody fragment discussed respect their characteristics binding ways them.

Language: Английский

Citations

5
Half‐life extension of single‐domain antibody–drug conjugates by albumin binding moiety enhances antitumor efficacy DOI Creative Commons
Quanxiao Li,

Yu Kong,

Yuxuan Zhong

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract Single‐domain antibody–drug conjugates (sdADCs) have been proven to deeper solid tumor penetration and intratumor accumulation capabilities due their smaller size compared with traditional IgG format ADCs. However, one of the key challenges for improving clinical outcomes sdADCs is abbreviated in vivo half‐life. In this study, we innovatively fused an antihuman serum albumin (αHSA) nanobody a targeting oncofetal antigen 5T4, conferring binding enhance pharmacokinetic profiles sdADCs. The fusion protein was conjugated monomethyl auristatin E (MMAE) at s224c site mutation. conjugate exhibited potent cytotoxicity against various cells. Compared nonalbumin‐binding counterparts, 10‐fold extended half‐life wild‐type mice fivefold prolonged BxPC‐3 xenograft models as well enhanced retention mice. Consequently, n501–αHSA–MMAE showed antitumor effects, which were comparable n501–MMAE pancreatic cancer models; however, human ovarian teratoma PA‐1 models, significantly improved efficacy. Moreover, mitigated hepatotoxicity. summary, our results suggested that albumin‐binding moiety viable strategy can therapeutic potential through optimized pharmacokinetics.

Language: Английский

Citations

4
PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies DOI Creative Commons
Neysha Martínez‐Orengo, Swati Shah, Jianhao Lai

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111795 - 111795

Published: Jan. 13, 2025

Radiolabeled antibodies against the HIV-1 envelope protein, gp120, have been previously tested in animal models and people with HIV (PWH). Nanobodies offer advantages over antibodies, including smaller size faster clearance, which allow labeling fluorine-18. In this study, three nanobodies (J3, 3E3, B9) chosen based on their binding properties to conserved CD4-binding site of gp120 were labeled fluorine-18 used for PET imaging mice bearing wild-type (WT) and/or gp120-expressing (Env+) tumors. [18F]J3 [18F]3E3 selectively targeted Env+ tumors not WT tumors, minimal background signal. Switching from non-site-specific radiolabeling method sortase A-mediated site-specific conjugation at C-terminus improved all nanobodies. Site-specifically 18F-labeled J3 nanobody is most promising candidate highest level binding. These results establish an that will enable next stage testing preclinical infection model potentially PWH.

Language: Английский

Citations

0